Novel ribosomal mutations affecting translational accuracy, antibiotic resistance and virulence of Salmonella typhimurium

Authors

  • Johanna Björkman,

    1. Department of Microbiology, The Biomedical Center, Box 581, Uppsala University, S-75123 Uppsala, Sweden, and The Swedish Institute for Infectious Disease Control, S-10521 Stockholm, Sweden.,
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  • Patrik Samuelsson,

    1. Department of Molecular Biology, The Biomedical Center, Box 590, Uppsala University, S-75124 Uppsala, Sweden.
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  • Dan I. Andersson,

    1. Department of Microbiology, The Biomedical Center, Box 581, Uppsala University, S-75123 Uppsala, Sweden, and The Swedish Institute for Infectious Disease Control, S-10521 Stockholm, Sweden.,
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  • Diarmaid Hughes

    1. Department of Molecular Biology, The Biomedical Center, Box 590, Uppsala University, S-75124 Uppsala, Sweden.
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Diarmaid Hughes. E-mail Hughes@alpha2.bmc.uu.se; Tel. (18) 471 42 03; Fax (18) 55 77 23.

Abstract

Many mutations in rpsL cause resistance to, or dependence on, streptomycin and are restrictive (hyperaccurate) in translation. Dependence on streptomycin and hyperaccuracy can each be reversed phenotypically by mutations in either rpsD or rpsE. Such compensatory mutations have been shown to have a ram phenotype (ribosomal ambiguity), increasing the level of translational errors. We have shown recently that restrictive rpsL alleles are also associated with a loss of virulence in Salmonella typhimurium. To test whether ram mutants could reverse this loss of virulence, we have isolated a set of rpsD alleles in Salmonella typhimurium. We found that the rpsD alleles restore the virulence of strains carrying restrictive rpsL alleles to a level close to that of the wild type. Unexpectedly, three out of seven mutant rpsD alleles tested have phenotypes typical of restrictive alleles of rpsL, being resistant to streptomycin and restrictive (hyperaccurate) in translation. These phenotypes have not been previously associated with the ribosomal protein S4. Furthermore, all seven rpsD alleles (four ram and three restrictive) can phenotypically reverse the hyperaccuracy associated with restrictive alleles of rpsL. This is the first demonstration that such compensations do not require that the compensating rpsD allele has a ribosomal ambiguity (ram) phenotype.

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